We have identified a mutation in the insulin-like growth factor receptor in residue 481 of the alpha subunit (extracellular domain) in a pediatric patient with growth retardation. We have created plasmids that express the normal receptor and the mutated receptor and have transfected NIH-3T3 cells with these plasmids to obtain clones to examine the functionality of the mutation. These studies will include IGF-I binding to the receptor and the activation of the tyrosine kinase activity to determine how this mutation affects skeletal growth.